Comparison of the Anti-Inflammatory Effects of Induced Pluripotent Stem Cell-Derived and Bone Marrow-Derived Mesenchymal Stromal Cells in a Murine Model of Corneal Injury

Cytotherapy. 2017 Jan;19(1):28-35. doi: 10.1016/j.jcyt.2016.10.007. Epub 2016 Nov 10.

Abstract

Background aims: Mesenchymal stromal cells (MSCs) offer tremendous potential for therapeutic applications for inflammatory diseases. However, tissue-derived MSCs, such as bone marrow-derived MSCs (BM-MSCs), have considerable donor variations and limited expandability. It was recently demonstrated that MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have less pro-tumor potential and greater expandability of homogenous cell population. In this study, we investigated the anti-inflammatory effects and mechanism of iPSC-MSCs in a murine model of chemical and mechanical injury to the cornea and compared the effects with those of BM-MSCs.

Methods: To create an injury, ethanol was applied to the corneal surface in mice, and the corneal epithelium was removed with a blade. Immediately after injury, mice received an intravenous injection of (i) iPSC-MSCs, (ii) BM-MSCs or (iii) vehicle. Clinical, histological and molecular assays were performed in the cornea to evaluate inflammation.

Results: We found that corneal opacity was significantly reduced by iPSC-MSCs or BM-MSCs. Histological examination revealed that the swelling and inflammatory infiltration in the cornea were markedly decreased in mice treated with iPSC-MSCs or BM-MSCs. Corneal levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were lower in iPSC-MSC- and BM-MSC-treated mice, compared with vehicle-treated controls. In contrast, iPSC-MSCs with a knockdown of the TNF-α stimulating gene (TSG)-6 did not suppress the levels of inflammatory cytokines and failed to reduce corneal opacity.

Conclusions: Together these data demonstrate that iPSC-MSCs exert therapeutic effects in the cornea by reducing inflammation in part through the expression of TSG-6, and the effects are similar to those seen with BM-MSCs.

Keywords: bone marrow; cornea; induced pluripotent stem cell; inflammation; mesenchymal stromal cells.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Corneal Injuries / metabolism
  • Corneal Injuries / therapy*
  • Corneal Opacity / pathology
  • Corneal Opacity / therapy
  • Disease Models, Animal
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / transplantation
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Keratitis / pathology
  • Keratitis / therapy
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Mice, Inbred BALB C
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cell Adhesion Molecules
  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • Tnfaip6 protein, mouse
  • Tumor Necrosis Factor-alpha